Effect of histamine on electrical and mechanical activity of the myocardial fibers of the guinea pig heart after blocking of the fast sodium channels

Vornovitskii, E. G.; Ignat'eva, V. B.; Bi, Khodorov

doi:10.1007/bf00804345

Cited by 5 publications

(2 citation statements)

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“…For instance, these types of channels are resistant to the action of TTX, they are blocked by Mn and Co ions and by verapamil and D-600, antagonists of Ca ++ , and the potential-dependence of their activation is shifted toward lower potentials with an increase in the external Ca ++ concentration [4,5]. There is also some similarity in the properties of the fast TTX-sensitive currents of neurons and cardiomyocytes [3,6].…”

Section: Resultsmentioning

confidence: 98%

“…A leading role in determination of the frequency of the cardiac pacemaker and amplitude of atrial contractions is known to be played by slow tetrodotoxin (TTX)-resistant sodium-calcium channelsof the inward current [5,14], and the duration of the refractory period of the electrically excitable membrane of cardiomyocytes depends on the rate of reaction of TTX-resistant and TTX-sensitive channels of the inward current [i0]. Neurons of the rat spinal ganglia have two types of inward current channels --slow and fast.…”

Section: Resultsmentioning

confidence: 99%

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Effect of the macrocyclic polyester 15-crown-5 on ionic permeability of excitable membranes

Bogatskii¹,

Luk’yanenko²,

Savenko³

et al. 1984

Bull Exp Biol Med

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The parmacology and biophysics of macrocyclic polyester complexones have been at the focus of attention of research workers in recent years [9, 16]. The use of these compounds as modulators of ionic permeability of excitable membranes is particularly interesting. It was shown in [16] that 15-crown-5 has a marked chronotropic and inotropic action on the isolated frog heart, which provides the basis for a search for new cardiotropic drugs in the macrocyclic polyester series.The aim of this investigation was to study the mechanism of action of 15-crown-5 on biological and model membranes. EXPERIMENTAL METHODThe strength and frequency of contraction of the isolated guinea pig atrium were recorded by means of a strain-gauge transducer, Topaz-2 amplifier, and N-3020-3 automatic writer.The velocity of contraction was estimated by means of a piezoelectric transducer. The signal from the transducer was recorded photographically from the oscilloscope screen. The refractory period of atrial contractions was determined by the method described previously [8]. Ionic currents of the electrically excitable membrane of isolated rat spinal ganglionic neurons were measured under intracellular dialysis and voltage clamp conditions by the method in [7]. The effect of 15-crown-5 on the surface potential of biomembranes was studied on a bimolecular lipid membrane (BLM) by a potentiodynamic method [i]. BLM was formed on the mouth of a small Teflon jar from a solution of phosphatidylcholine in decane (40 mg/ml). EXPERIMENTAL RESULTSPolyester 15-crown-5 in a concentration of 5-i0-~-i0 -3 M did not affect the force of contraction of the isolated rat heart but reduced the frequency of its contractions.A similar effect was observed on the isolated guinea pig atrium (Fig. i). The negative chronotropic action of the polyester on the atrium was combined with lengthening of the refractory period of its contractions (Fig. i) and a decrease in the velocity of the contractions.In a concentration of 10 -3 M it reduced the velocity by 48%.In the same concentrations 15-crown-5 did not affect the chronotropic reactions of the heart to acetylcholine and adrenalin and its action was unchanged in the presence of atropine and Inderal (propranolol).As a first approximation the action of 15-crown-5 on the heart of warm-blooded animals can thus be reduced to a change in the parameters of excitability of the sinuatrial node.Because of the high stability constant of complexes of 15-crown-5 with ions of the alkaline earth metals in water [Ii], it can be postulated that some of the effects of the compound described above on the atrium may be sensitive to Ca ++ concentration.In fact 15-crown-5, in a concentration of 2"10 -4 M, abolished the action of Ca ++ on the refractory period of contractions of the guinea pig atrium.Simple calculations show that the decrease in the Ca++ concentration in physiological saline on account of complex formation with 15-crown-5 did not exceed 5%. Judging from the relationship between the action of Ca++ and its *Deceased.

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Section: Resultsmentioning

confidence: 98%

Section: Resultsmentioning

confidence: 99%

Effect of the macrocyclic polyester 15-crown-5 on ionic permeability of excitable membranes

Bogatskii¹,

Luk’yanenko²,

Savenko³

et al. 1984

Bull Exp Biol Med

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Restoration by histamine of the calcium-dependent electrical and mechanical response in the guinea-pig papillary muscle partially depolarized by potassium

Inui¹,

Imamura²

1976

Naunyn-Schmiedeberg's Arch. Pharmacol.

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Electrophysiological and mechanical effects of histamine were observed in guinea-pig papillary muscle which had been depolarized and rendered inexcitable by elevation of potassium concentration in Tyrode solution to 27 mM. 1. Histamine (3 X 10(-7) to 3 X 10(-5) M) restored the action potential and tension development. The amplitude of the action potential was increased by 31.6 mV/10-fold increase in extracellular Ca2+ concentration. Nifedipine (10(-6) M) abolished the electrical and mechanical responses which had been restored by histamine (10(-5) M) but TTX (10(-5) M) did not affect them. Reduction of the extracellular Na+ concentration to one half decreased the amplitude and the maximum rate of rise of the action potential restored by histamine (10(-5) M) while the peak tension was increased and an after-contraction occurred. 2. The maximum rate of rise and the amplitude of the action potential restored by histamine (10(-5) M) decreased with increase in stimulus frequency from 0.1-1.6 Hz. The peak tension decreased and then increased. The shape of the developed tension was also changed. In the presence of caffeine (1 mM), the only effect of an increase in stimulus frequency was a decrease in peak tension but the change in the shape of developed tension did not occur. 3. The electrical and mechanical responses restored by histamine (3 X 10(-6) or 10(-5) M) were depressed by metiamide (3 X 10(-6) M) but not by diphenhydramine (10(-5) M) or bufetolol (10(-6) M). 4. The electrical response restored by histamine (10(-6) or 10(-5) M) was enhanced by papaverine (10(-5) M) and depressed by N-methylimidazole (10 mM). It is concluded that histamine may enhance the slow inward Ca2+ current mediated by histamine H2-receptors and the adenylate cyclase system in ventricular muscle and that the positive inotropic action of histamine may be attributed to these mechanisms.

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Mechanism of the histamine-induced positive inotropic action in cardiac muscle

Josephson

Renaud

Vogel

et al. 1976

European Journal of Pharmacology

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Effect of histamine on electrical and mechanical activity of the myocardial fibers of the guinea pig heart after blocking of the fast sodium channels

Cited by 5 publications

References 4 publications

Effect of the macrocyclic polyester 15-crown-5 on ionic permeability of excitable membranes

Effect of the macrocyclic polyester 15-crown-5 on ionic permeability of excitable membranes

Restoration by histamine of the calcium-dependent electrical and mechanical response in the guinea-pig papillary muscle partially depolarized by potassium

Mechanism of the histamine-induced positive inotropic action in cardiac muscle

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